title: MiR-503 regulates osteoclastogenesis via targeting RANK.
abstract: MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. However, no study has investigated the role of miRNA in postmenopausal osteoporosis. Here, we report that miR-503 was markedly reduced in circulating progenitors of osteoclasts-CD14(+) peripheral blood mononuclear cells (PBMCs) from postmenopausal osteoporosis patients compared with those from postmenopausal healthy women. Overexpression of miR-503 in CD14(+) PBMCs inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Conversely, silencing of miR-503 in CD14(+) PBMCs promoted osteoclastogenesis. RANK, which is activated by the binding of RANKL and inducing osteoclast differentiation, was confirmed to be a target of miR-503. In vivo, silencing of miR-503 using a specific antagomir in ovariectomy (OVX) mice increased RANK protein expression, promoted bone resorption, and decreased bone mass, whereas overexpression of miR-503 with agomir inhibited bone resorption and prevented bone loss in OVX mice. Thus, our study revealed that miR-503 plays an important role in the pathogenesis of postmenopausal osteoporosis and contributes to a new therapeutic way for osteoporosis.
authors.affiliation: Institute of Endocrinology & Metabolism, The Second Xiangya Hospital of Central South University, Changsha, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhou
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Wu
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
authors.forename: Xiang-Hang
authors.initials: XH
authors.lastname: Luo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D018950:Lipopolysaccharide Receptors; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D015663:Osteoporosis, Postmenopausal / Q000235:genetics / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D018950:Lipopolysaccharide Receptors; C545473:MIRN503 microRNA, human; D035683:MicroRNAs; C556275:Mirn503 microRNA, mouse; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505687:Tnfrsf11a protein, mouse
keywords: OSTEOCLASTOGENESIS; OSTEOPOROSIS; PBMCs; RANK; microRNA